Platelet Membrane-Coated Nanoparticles Target Sclerotic Aortic Valves in ApoE-/- Mice by Multiple Binding Mechanisms Under Pathological Shear Stress

血小板膜包被的纳米粒子在病理剪切应力下通过多种结合机制靶向 ApoE-/- 小鼠的硬化主动脉瓣

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作者:Hongbo Yang #, Yanan Song #, Jing Chen #, Zhiqing Pang, Ning Zhang, Jiatian Cao, Qiaozi Wang, Qiyu Li, Feng Zhang, Yuxiang Dai, Chenguang Li, Zheyong Huang, Juying Qian, Junbo Ge

Background

Aortic valve disease is the most common valvular heart disease leading to valve replacement. The efficacy of pharmacological therapy for aortic valve disease is limited by the high mechanical stress at the aortic valves impairing the binding rate. We aimed to identify nanoparticle coating with entire platelet membranes to fully mimic their inherent multiple adhesive mechanisms and target the sclerotic aortic valve of apolipoprotein E-deficient (ApoE-/-) mice based on their multiple sites binding capacity under high shear stress.

Conclusion

PNPs could provide a promising platform for the molecular diagnosis and targeting treatment of aortic valve disease.

Methods

Considering the potent interaction of platelet membrane glycoproteins with components present in sclerotic aortic valves, platelet membrane-coated nanoparticles (PNPs) were synthetized and the binding capacity under high shear stress was evaluated in vitro and in vivo.

Results

PNPs demonstrated effectively adhering to von Willebrand factor, collagen and fibrin under shear stresses in vitro. In an aortic valve disease model established in ApoE-/- mice, PNPs exhibited good targeting to sclerotic aortic valves by mimicking platelet multiple adhesive mechanisms.

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